1. Field of the Invention
The present invention relates generally to the fields of virology, immunology and pathology. More particularly, it concerns the development of human monoclonal antibodies for use in the diagnosis, prevention and therapy of respiratory syncytial virus infections.
2. Description of Related Art
Human respiratory syncytial (RSV) virus is a pneumovirus in the family Paramyxoviridae. It is a non-segmented negative-strand RNA virus, with a cytoplasmic replication program. The viral nucleocapsid is packaged in a lipid envelope that is acquired from the host cell plasma membrane during budding. The virus has a fusion protein (RSV F) and a highly glycosylated attachment G glycoprotein (RSV G). RSV can infect cells as a cell-free virus, but can also spread by syncytium formation between infected cells and uninfected neighboring cells. Membrane fusion is important for both virus entry and for cell-to-cell spread.
RSV is the leading viral cause of severe lower respiratory tract illness in infants and young children (Walsh and Graham, 1999). RSV can also cause severe illness and death in the elderly (Treanor and Falsey, 1999) and immunocompromised bone marrow (Hertz et al., 1989; Wendt et al., 1995) and lung transplant patients (Wendt et al., 1995). The mortality rate in bone marrow transplant patients has been reported to be between 70 and 100% (Hertz et al, 1989).
Although RSV-induced disease in infants may be primarily immune-mediated, in bone marrow and lung transplant recipients and in persons with severe combined immunodeficiency syndrome the pathology, characterized by giant cell formation, is related to ongoing viral replication. In addition, infants with AIDS have been shown to have continuous viral shedding for over 200 days (King et al., 1993). These patient groups would benefit from more effective antiviral therapeutic options for RSV, and it is even more likely that antiviral prophylaxis would have an impact on illness in infants and the elderly.